Cellular basis of abnormal calcium transients of failing human ventricular myocytes

Valentino Piacentino, Christopher R. Weber, Xiongwen Chen, Jutta Weisser-Thomas, Kenneth B. Margulies, Donald M Bers, Steven R. Houser

Research output: Contribution to journalArticle

327 Citations (Scopus)

Abstract

Depressed contractility is a central feature of the failing human heart and has been attributed to altered [Ca2+]i. This study examined the respective roles of the L-type Ca2+ current (ICa), SR Ca2+ uptake, storage and release, Ca2+ transport via the Na+-Ca2+ exchanger (NCX), and Ca2+ buffering in the altered Ca2+ transients of failing human ventricular myocytes. Electrophysiological techniques were used to measure and control Vm and measure Im, respectively, and Fluo-3 was used to measure [Ca2+]i in myocytes from nonfailing (NF) and failing (F) human hearts. Ca2+ transients from F myocytes were significantly smaller and decayed more slowly than those from NF hearts. Ca2+ uptake rates by the SR and the amount of Ca2+ stored in the SR were significantly reduced in F myocytes. There were no significant changes in the rate of Ca2+ removal from F myocytes by the NCX, in the density of NCX current as a function of [Ca2+]i, ICa density, or cellular Ca2+ buffering. However, Ca2+ influx during the late portions of the action potential seems able to elevate [Ca2+]i in F but not in NF myocytes. A reduction in the rate of net Ca2+ uptake by the SR slows the decay of the Ca2+ transient and reduces SR Ca2+ stores. This leads to reduced SR Ca2+ release, which induces additional Ca2+ influx during the plateau phase of the action potential, further slowing the decay of the Ca2+ transient. These changes can explain the defective Ca2+ transients of the failing human ventricular myocyte.

Original languageEnglish (US)
Pages (from-to)651-658
Number of pages8
JournalCirculation Research
Volume92
Issue number6
DOIs
StatePublished - Apr 4 2003
Externally publishedYes

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Muscle Cells
Calcium
Action Potentials

Keywords

  • Congestive heart failure
  • Excitation-contraction coupling
  • Na-Ca exchanger
  • Sarcoplasmic reticulum

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Piacentino, V., Weber, C. R., Chen, X., Weisser-Thomas, J., Margulies, K. B., Bers, D. M., & Houser, S. R. (2003). Cellular basis of abnormal calcium transients of failing human ventricular myocytes. Circulation Research, 92(6), 651-658. https://doi.org/10.1161/01.RES.0000062469.83985.9B

Cellular basis of abnormal calcium transients of failing human ventricular myocytes. / Piacentino, Valentino; Weber, Christopher R.; Chen, Xiongwen; Weisser-Thomas, Jutta; Margulies, Kenneth B.; Bers, Donald M; Houser, Steven R.

In: Circulation Research, Vol. 92, No. 6, 04.04.2003, p. 651-658.

Research output: Contribution to journalArticle

Piacentino, V, Weber, CR, Chen, X, Weisser-Thomas, J, Margulies, KB, Bers, DM & Houser, SR 2003, 'Cellular basis of abnormal calcium transients of failing human ventricular myocytes', Circulation Research, vol. 92, no. 6, pp. 651-658. https://doi.org/10.1161/01.RES.0000062469.83985.9B
Piacentino, Valentino ; Weber, Christopher R. ; Chen, Xiongwen ; Weisser-Thomas, Jutta ; Margulies, Kenneth B. ; Bers, Donald M ; Houser, Steven R. / Cellular basis of abnormal calcium transients of failing human ventricular myocytes. In: Circulation Research. 2003 ; Vol. 92, No. 6. pp. 651-658.
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